For 20 years, Bristol's Dental Clinical Trials Unit has worked in
partnership with industrial sponsors
to develop a dental model to evaluate products designed to protect teeth
from erosion and
abrasion, and to test whether new toothpastes block dentine tubules,
thereby reducing pain from
sensitive teeth. This model is used by researchers worldwide and is the
"gold standard". New
toothpastes launched by GSK, Colgate, Unilever and P&G between 2008
and 2013, tested with the
dental model, demonstrably reduce dentine hypersensitivity. These
toothpastes are sold in
advanced and emerging markets in over 100 countries, with sales of £5bn in
2012.

Underpinning research

The Bristol Dental Clinical Trials Unit (CTU) developed the intra-oral
appliance model [1] initially
to investigate the aetiological factors of dentine hypersensitivity (DH),
abrasion and erosion on
human tooth samples retained in the mouth. The model enabled the
development of low-erosive,
low-abrasive products to protect teeth and the evaluation of toothpastes
for their acid-resistant
occlusion ability to treat DH and reduce pain. DH's global prevalence is
growing as more people
retain healthy teeth for life and increasingly consume "healthy" yet
erosive diets, eliciting frequent
DH episodes as tooth-wear opens dentine tubules. A partnership was formed
between the CTU
and industry to address this issue using the Bristol model.

In 1994, pioneering CTU research led by Professor Addy (1994-2007) and
supported by Dr West
(Lecturer, 1994-2004; Senior Lecturer 2004-2009) developed the intra-oral
appliance model
allowing human tooth samples to be retained in volunteers' mouths. The
model permits samples
to be tested clinically rather than in the laboratory [1]. Historically,
laboratory testing produced
indicative results but could not replicate the mouth's complex intra-oral
environment. This was a
major obstacle to assessing product effectiveness.

The original upper appliance [1] proved it was possible to differentiate
degrees of tooth erosion
from acidic drinks, leading to the development and marketing of Ribena
ToothKind [2]between
1994 and 2000, demonstrating the model's reproducibility [7]. This was the
first acidic drink
proven to have reduced erosive potential compared to marketed competitors
[2]. A series of
clinical studies followed, improving the stability and taste of the drink
by varying calcium and
phosphate, whilst maintaining low erosive properties. The methodology was
audited
independently, with the product gaining British Dental Association
approval. Proof of concept of
the model was achieved. Following the development of Ribena ToothKind,
carbonated and sports
drinks were modified and evaluated in the model, with positive results.
Erosion of deciduous teeth
was compared to adult teeth, the former being more susceptible. The next
step in the strategy
(2003-2004 [8]) was to investigate the protective effects of toothpastes
against tooth erosion. The
results using the model were very positive.

Professor West commenced leadership of the CTU in 2007 (Senior Lecturer
2004-2009;
Professor 2009-present) with a series of clinical studies (2007-2010 [9])
identifying low-abrasive
toothpastes which did not open dentine tubules on application [3] and new
pastes which
protected teeth from erosive dietary challenge [4]. The appliance was
improved, allowing
multiple-sample positioning in upper [4] and lower dental [3] appliances.
New designs permitted
more samples to be retained in the mouth, with removal and replacement at
any point in the
study for treatment and measurement [3, 4]. This allowed the CTU and
sponsors to develop low-
abrasive pastes and toothpastes affording erosion resistance to teeth.

A further research programme led by Professor West using the dental model
in clinical studies
(2009-2012 [10]), developed and confirmed new desensitising toothpastes
which blocked open
dentine tubules more effectively than control toothpastes [5]. Following
the success of toothpaste
occlusion technologies using the dental model [5], these desensitising
toothpaste products were
subsequently evaluated in randomised control trials and gave immediate and
prolonged pain relief
from DH [6].

Details of the impact

Link between research and impact

The CTU model was the first intra-oral model to measure tooth-wear [1],
with development and
refinement [2, 3, 4, 5] revolutionising research methodologies on
reduction of tooth-wear, and the
first to measure intra-oral tubule occlusion. In 2010, world dental
leaders were invited to a DH
symposium in Geneva, with the consensus being that in situ erosion models
with an intra-oral
acidic challenge are the ideal [a]. Unilever commented that "the CTU
developed an intra-oral
appliance retaining human tooth tissue which was a breakthrough novel
technology in this area"
[b].

This research has enabled new desensitising toothpastes with proven
efficacy in DH pain reduction
to be licensed. GlaxoSmithKline (Rapid Relief, Repair and Protect,
Pronamel) [c], Procter and
Gamble (Oral B Pro Expert/Health) [d] and Colgate Palmolive (Pro Relief)
launched products
between 2008 and 2012, having tested toothpastes using the intra-oral
model. The Bristol
methodology has helped to protect teeth from tooth-wear and reduce pain
from DH worldwide.

Nature and extent of the impact

Since the introduction of the model [1], it has been employed by many
research groups worldwide
[e, f] and has had a huge impact on the evaluation of products for
tooth-wear and tubule occlusion.
The model permits products that are effective in the laboratory to be
tested in real-world conditions
to determine whether the theoretical results translate into real effects.
Best-practice product-testing
now consists of laboratory testing, clinical testing using the model and
randomised control trial
human pain studies, correlating methodologies to strengthen the
significance of the observed
results [5, 6].

Photographs of teeth showing occluded dentine tubules, taken following
research using the model,
feature in promotional and educational guidance for the public and dental
professionals, as well as
in sponsor' in-house training. Television advertisements use graphics
illustrating occluded tubules
to explain the physical effect of the toothpastes and pain reduction. The
sponsor companies use
this literature worldwide.

Professor West was invited to speak at 22 international symposia on DH
between 2007 and 2013
for GSK (18 symposia [c]), P&G and Colgate-Palmolive and is on
advisory groups for GSK [c] and
P&G. She was a keynote speaker at the launch of desensitising
toothpastes developed using the
CTU intra-oral model for Repair and Protect and Rapid Relief (GSK),
Pro-Relief (Colgate) and Oral
B Pro Expert (P&G).

Industrial development benefits of the impact

Researchers now have the ability to develop products quickly and test them
in a reliable and
consistent way to show dentine tubule occlusion. The model has been
adopted globally and used
by sponsors such as GSK [c], P&G [d], Colgate and Unilever [b] at
international research sites.
GSK comments that "following this methodological development and
understanding, the Bristol
Clinical Trials Unit intra-oral appliance for in situ clinical trials, is
now routinely used to assess the
ability of toothpastes to block open dentine tubules" [c]. Professor West
has been influential in
changing industrial practice in product development, resulting in the
recent successful launch and
high global sales of desensitising toothpastes, affecting millions of
people worldwide [b, c, d, g, h,
i]. In Europe, over 40% of the population experience tooth-wear and DH
[j]. These new toothpastes
address this problem.

Commercial benefits of the impact to industry

Research on DH using the model, has underpinned science-led global
marketing with high sales of
Sensodyne toothpastes for GSK (Rapid Relief, Pronamel and Repair and
Protect) to relieve DH
pain [c]. GSK desensitising toothpastes are available in over 100
countries with a turnover in 2011/
2012 of £1.7bn, making relief from sensitive teeth available to a global
population [c, g, h]. GSK
has recently relaunched Ribena ToothKind as Ribena Light, with low-erosive
drinks sales worth
£1bn in 2011. Sensodyne Rapid Relief was launched in 2010 and Sensodyne
Repair & Protect in
2011. The latter has attracted almost 2.3m households and is worth £15.7m
of the UK sensitive-
toothpaste market [h]. It achieved a 4% share of the total toothpaste
market and became the
number one selling toothpaste in the first 16 weeks of sales [h].
Sensodyne product sales rose by
16% in 2011 and 13% in 2012, with strong growth in emerging markets such
as Africa, China and
India. Similarly, Lucozade and Ribena sales were up by 10% in 2011 [g]. In
2012, Sensodyne
Repair and Protect became GSK's first billion-dollar brand [g]. Repair
& Protect was awarded
Product of The Year for 2013. Product of the Year is the world's largest
independent, consumer-
voted award for product innovation [h].

Similarly, the CTU's work with P&G (2007-2010) led to the marketing
of an occluding product, Oral
B Pro Expert/Health - a desensitising paste with the ability to protect
tooth tissue from erosive acid
challenge and block dentine tubules [d, i]. P&G have the
second-leading brand in desensitising
toothpaste, with a 20% share of the market, again benefiting millions of
people worldwide [d,i].

[b] Letter of support from Unilever, Global Clinical Leader Oral Care,
Unilever R&D, Bebington,
Wirral, UK. This letter confirms the successful use of the model by
Unilever in collaboration
with Professor West's research group to develop toothpastes that protect
against tooth wear
and reduce the pain of dentine hypersensitivity, with global market
sales.

[c] Letter of support from GSK, Medical Director Consumer Health Care,
Weybridge, Surrey, UK.
This letter confirms the successful use of the model by GSK in
collaboration with Professor
West's research group to develop toothpastes and provides examples of
these, together with
an overview of their global market sales. It also confirms that
Professor West is an
international researcher in toothwear and dentine hypersensitivity
frequently speaking in the
international forum and advising GSK in advisory groups.

[d] Letter of support from P&G, Clinical Director, P&G, Oral Care
Clinical Operation, P&G, Mason
Business Centre, 8700 Mason-Montgomery Rd, Mason, OH 45040, USA.This letter confirms that P&G has collaborated with Professor West
and used the intra-oral
model to successfully develop toothpastes that protect against tooth
wear. Examples of
toothpastes developed using this model, and sales figures for these are
provided.

[f] Schlueter, N., Klimek, J. & Ganss, C.(2009) `Efficacy of an
Experimental Tin-F-Containing
Solution in Erosive Tissue Loss in Enamel and Dentine in situ', Caries
Research, 43 (6): 415-
421. http://www.karger.com/Article/FullText/252974
This article published by an independent group based in Germany
supports the use of the
Bristol intra-oral appliance for tooth wear research by other research
groups.

[i] P&G Annual Report 2012. This report demonstrates P&G are
number two in global market
share position in Oral Healthcare, and identify increase in sales in
2012 with expansion of the
Oral B Pro Expert/Health sensitivity toothpaste range developed using
the model. See
brochure pages 27 and 35.

[j] West, N., Sanz, M., Lussi, A., Bartlett, D., Bouchard, P. &
Bourgeois, D. (2013) `Prevalence of
dentine hypersensitivity and study of associated factors: a European
population-based cross-
sectional study'. Journal of Dentistry 41(10):841-851.http://dx.doi.org/10.1016/j.jdent.2013.07.017.
This article demonstrates a high incidence of
dentine hypersensitivity in young European adults, over 40%, supporting
the need for the
development of toothpastes that are better at reducing toothwear and
pain from sensitive teeth.
The intra-oral model will continue to provide impact as it is used in
studies to test the efficacy of
such toothpastes.